A Phase 1, First-in-Human, Single-center, Randomized, Double-masked, Placebo-controlled Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Single and Multiple Ascending Doses of MDI-1228_mesylate Ophthalmic Solution by Local Instillation in Adult Healthy Volunteers

MDI-1228-I-AC

The main goal of this clinical trial is to evaluate the safety, tolerability and pharmacokinetics (PK) profiles\* of MDI-1228_mesylate Ophthalmic Solution in healthy adult participants. Participants will receive either of the following treatment: * MDI-1228_mesylate Ophthalmic Solution, or * Placebo\*\* Researchers will observe any changes in heath (if any) in participants receiving the study treatment to evaluate the safety and tolerability\*\*\* of the study drug. Researchers will also collect several blood samples from participants to study PK profiles of the drug. Note: * PK profiles: how the drug interacts with the body. \*\*placebo: a harmless substance that contains no active agents. \*\*\*tolerability: how well you can tolerate the drug.

2023-10-06

2024-07-01

2024-10-01

Recruiting

Early phase I

40

Inclusion Criteria: 1. Weight ≥ 50 kg for males, ≥ 45 kg for females, with the BMI (BMI = weight\[kg\]/height\[m\]2) between 18 and 32 (inclusive) at screening. 2. The corrected visual acuity (CVA) of both eyes should be 6/6 or 20/20 (Snellen chart), with an intraocular pressure between 10 and 21 mmHg (inclusive) and a difference in intraocular pressure between the 2 eyes \< 5 mmHg at screening. 3. Normal vital signs after ≥ 5 minutes resting supine or semi supine position: 1. ≥ 90 mmHg and ≤160 mmHg (systolic blood pressure) 2. ≥50 mmHg and ≤ 95 mmHg (diastolic blood pressure) 3. ≥ 45 beats per minute (bpm) and ≤ 100 bpm (heart rate) 4. Body temperature ≥35.5℃ and ≤37.7℃ 5. Respiratory Rate≥12 breaths/minute and≤22 breaths/minute 4. Standard 12-lead ECG parameters after ≥5 minutes resting in supine or semi-supine position with PR ≥ 120 ms and ≤ 220 ms, QRSD \< 120 ms, QTcF ≤ 450 ms for males and ≤ 470 ms for females, and otherwise normal ECG (all data limits are based on average readings of the ECGs) at screening. 5. Females must be non-pregnant and non-lactating, and either surgically sterile (e.g., tubal occlusion, hysterectomy, bilateral salpingectomy, bilateral oophorectomy), or use highly effective contraceptive method as assessed by the PI (OCPs, long-acting implantable hormones, injectable hormones, a vaginal ring or an IUD) from screening until study completion, including the follow up period for at least 30 days after the last dose of study drug, or be post-menopausal for ≥ 12 months. Post-menopausal status will be confirmed through testing of follicle-stimulating hormone (FSH) levels at screening for amenorrheic female participants. Females who are abstinent from heterosexual intercourse as part of their usual lifestyle will also be eligible for participation. 6. Women of childbearing potential (WOCBP) must have a negative pregnancy test at screening and admission and be willing to have additional pregnancy tests as required throughout the study. 7. Males must be surgically sterile (\> 30 days since vasectomy with no viable sperm), abstinent, or if engaged in sexual relations with a WOCBP, the participant and his partner must be surgically sterile (e.g., tubal occlusion, hysterectomy, bilateral salpingectomy, bilateral oophorectomy) or using an acceptable, highly effective contraceptive method as assessed by the PI from screening until study completion, including the follow up period, for at least 30 days after the last dose of study drug. Acceptable methods of contraception include the use of condoms and the use of an effective contraceptive for the female partner (WOCBP) that includes: OCPs, long- acting implantable hormones, injectable hormones, a vaginal ring, or an IUD. Male participants whose female partner is post-menopausal, and participants who are abstinent from heterosexual intercourse as part of their usual lifestyle and are not planning to conceive will also be eligible. 8. Male participants must agree to refrain from donating sperm and female participants from donating ova from screening until study completion, including the follow up period, for at least 90 days after the last dose of study drug. 9. Provides written informed consent and is willing and able to undergo all study procedures and attend the scheduled follow up visit/s per protocol. 10. Are willing to consume clinical research unit (CRU) provided meals. 11. Have no neck or back issues which prevents the participant having their head tilted back for dosing at the discretion of the Investigator. 12. Males and females aged 18 to 55 years old (inclusive) 13. Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, safety laboratory tests, and ECG. A potential participant with a clinical abnormality or laboratory parameters outside the normal reference range for the population being studied may be included only if the Investigator considers that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. The Investigator may discuss with the local MM and Sponsor MM as required. 14. Have no abnormal results or abnormal not clinically significant (as determined by the Investigator) results of ocular examinations of both eyes (including slit-lamp examination, corneal fluorescein staining test, light response pupil test, extraocular movement test, dilated fundus examination) Exclusion Criteria: 1. Have a current or past history of clinically significant circulatory system diseases, respiratory disorders, hepatobiliary disorders, digestive disorders, urinary system diseases, renal disorders, endocrine disorders, immune system disorders, malignancies, metabolic disorders, mental disorders, or nervous system diseases that, in the opinion of the Investigator, might confound the results of the study or pose an additional risk to the participant by virtue of their participation in the study. Participant with a history of uncomplicated kidney stones (defined as spontaneous passage and no recurrence in the last 5 years); uncomplicated cholecystectomy; Gilbert's syndrome; a past history of being treated by non-current depression may be enrolled in the study at the discretion of the Investigator. Participants with a history of childhood asthma (without hospitalization) that has symptomatically resolved and remains untreated may participant. 2. Have healed eye disorders (such as infection, trauma) in either eye within 1 month prior to the first dose. 3. Have a history of intraocular surgery and laser eye surgery in either eye. 4. Used any ocular products (including various eye drops or eye gel) within 14 days or 5 half-lives (whichever is longer) prior to screening. 5. Wore contact lenses within 2 days prior to baseline (Day -1) or need to wear contact lenses throughout the clinical study. 6. Current evidence or history of COVID-19 or influenza-like illness as defined by fever (\> 37.7°C) and 2 or more of the following symptoms within 7 days before dosing: cough, sore throat, runny nose, sneezing, limb/joint pain, headache, vomiting/diarrhea in the absence of a known cause, other than influenza or COVID-19 infection. 7. A positive pre-study HIV, Hepatitis B surface antigen or positive Hepatitis C antibody result at screening. 8. Participants who are intolerant of venipuncture blood collection or have poor venous access and/or have a history of fear of needles and hemophobia. 9. Used Janus kinase (JAK) inhibitors or immunosuppressants or any other prescription drugs, traditional Chinese medicines or Chinese patent medicines within 4 weeks prior to Day -1; or used over-the-counter (OTC) drugs or health products within 2 weeks prior to Day -1, unless with a washout period of more than 5 half-lives for products with a longer half-life. The Principal Investigator may review medication on a case-by-case basis to determine if its use would compromise participant safety or interfere with study procedures or data interpretation. 10. Was vaccinated within 2 weeks prior to screening or plan to be vaccinated during the study. 11. Had major surgery within 6 months prior to screening or plan to undergo surgery during the study. 12. Participants who smoked more than 5 cigarettes/pipes/vaping per day on average or excessive use of any nicotine product (\> 5 products on average per day) within 3 months prior to screening and not able to abstain from smoking from screening to end of study (EoS). 13. Any other serious medical condition or abnormality that, in the Investigator's judgment, precludes the participant's safe participation in and completion of the study. 14. A positive pre-study drug or alcohol screen. A positive drug or alcohol screen test result may be verified by re-testing (up to 1 false positive result permitted) and may be followed up at the discretion of the Investigator. 15. History of regular alcohol consumption within 6 months of the study defined as an average weekly intake of \> 21 units for males or \> 14 units for females. One unit is equivalent to 10 g of alcohol and the following can be used as a guide: a half-pint (\~240 mL) of beer, 1 glass (125 mL) of wine or 1 (30 mL) measure of spirits. 16. The participant is unwilling to abstain from alcohol consumption from 24 hours prior to dosing until discharge from the CRU, and for 24 hours prior to all other outpatient visits to the CRU. 17. Known history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric, human or humanized antibodies, fusion proteins, MDI-1228_mesylate Ophthalmic Solution excipients, any material used for assessments (e.g., fluorescein, tropicamide, etc), or a history of drug or other allergy including severe allergic reaction that in the opinion of the Investigator contraindicates their participation. 18. Participation in a clinical trial within 30 days before randomization; use of any experimental therapy within 30 days or 5 half-lives prior to randomization, whichever is greater; or use of any biologic therapy within 12 weeks or 5 half-lives prior to randomization, whichever is greater. 19. Pregnant or breastfeeding WOCBP. 20. Donation within the last 3 months of \> 499 mL whole blood or within 2 weeks of any volume of plasma. 21. Participant unable to provide written informed consent or participant under guardianship. 22. Unwilling or unable to follow protocol requirements, including attendance at follow up visit/s. 23. Any history of severe ocular trauma in either eye at any time. 24. Any history of any refractive surgery procedure within the past 6 months of the screening visit in either eye. 25. Current or chronic history of clinically significant ocular disease within the past 3 months of screening visit in either eye. 26. Current or chronic history of ocular infection (bacterial, viral, or fungal) or corneal irritation within the past 3 months of screening visit in either eye. 27. Abnormal tearing, OR expected regular use of prescription or expected use of OTC tear substitutes within 4 weeks prior to Day -1, and for the duration of the study. 28. Previous or expected use of ocular (topical, periocular, intravitreal), local (inhaled or nasal), or systemic steroid or glucocorticoid medications within 4 weeks prior to Day -1, and for the duration of the study. 29. At the Investigator's or delegate's discretion, any participants who have a history of any significant ocular conditions in either eye that would contraindicate the use of the study medication, or that might affect the study conduct, or the interpretation of the study results. 30. Clinically significant findings as determined by the Investigator in other ocular examinations (e.g., conjunctival hyperemia grade \>1, corneal fluorescein staining score ≥ 2, or other chronic or acute eye disorders). 31. History of clinically significant ocular disease (glaucoma, retinal detachment, iritis, uveitis, herpetic keratitis, etc.) that, in the opinion of the Investigator, might confound the results of the study or pose an additional risk to the participant by virtue of their participation in the study. 32. Presence of an ocular pathology such as blepharitis, conjunctivitis, uveitis, or any other ocular infection or inflammation.

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE1'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'SEQUENTIAL', 'interventionModelDescription': 'This study consists of two parts:\n\n* Part A: Single ascending dose in healthy volunteers\n* Part B: Multiple ascending doses in healthy volunteers\n\nThe randomization code and the randomization list will be generated using SAS version 9.4 or the latest available version at time of randomization.', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'DOUBLE', 'whoMasked': ['PARTICIPANT', 'INVESTIGATOR']}}, 'enrollmentInfo': {'count': 40, 'type': 'ESTIMATED'}}

2024-01-16